GSK hep B treatment’s efficacy slips 60% in full phase 2 readout, but phase 3 going ahead

The efficacy of GSK's hepatitis B treatment may have dropped by over 60% between the interim and end-of-study analysis, but the Big Pharma is still hopeful the antisense oligonucleotide treatment will provide a functional cure for the infection.

The end-of-study results from the B-Clear phase 2b trial showed that 9% of patients with chronic hepatitis B on stable nucleoside/nucleotide analogues (NA) treatment and 10% of those not on NA treatment achieved the study’s primary outcome of a sustained clearance of their hepatitis B surface antigen levels and hepatitis B virus (HBV) DNA levels. Patients received 24 weeks of treatment with a 300 mg weekly dose.

Today’s readout, presented at the American Association for the Study of Liver Diseases’ Meeting, follows far more impressive initial data on bepirovirsen from June, which showed that 28 to 29% of participants had undetectable levels of the virus after 24 weeks. It’s not entirely clear what led to such a gap between the two readouts, although GSK told Fierce Biotech in an email that “as expected” some participants relapsed after the end of treatment, meaning their infection had since increased to detectable levels.

And even a 10% effectiveness rate among patients is around tenfold higher than the current standard of care, GSK pointed out in their email.

The company also pointed to a subgroup who the data suggests would benefit most from the treatment. Of patients with low baseline hepatitis B surface antigen levels, 16% who were also taking NAs saw a clearance of detectable levels of the virus and 25% of those not on NAs achieved this.

Longer term durability of response will be investigated in the B-Sure trial, which will follow participants for an additional 33 months and investigate whether by stopping other treatments bepirovirsen can be shown to be a functional cure in hep B patients.

“Today’s results from the B-Clear study are a promising step forward for the approximately 300 million people living with chronic hepatitis B,” Chris Corsico, SVP of Development at GSK, said in a Nov. 8 release. “We look forward to confirming these findings for bepirovirsen in our phase 3 study starting next year, as well as exploring potential sequential therapy options with the aim of helping more people living with [chronic hepatitis B] achieve functional cure.”

Currently, the hepatitis B treatment toolkit centers on interferon-type molecules and NAs such as entecavir, tenofovir disoproxil fumarate and tenofovir alafenamide. Interferon molecules boost the immune system, and NAs stop or slow replication of the virus. Yet, even when used in combination, only a small percentage of patients have undetectable levels of hepatitis B surface antigen—what is known as achieving functional cure.

GSK, having paid Ionis Pharmaceuticals $25 million upfront in 2019 for its hepatitis B program, is one of a set of companies trying to ramp up the percentage of patients with undetectable levels of the antigen. The company said today that it plans to launch a phase 3 trial for bepirovirsen next year, alongside ongoing phase 2 trials to explore potential sequential treatment options.